Structural and biochemical characterization of a nucleotide hydrolase from Streptococcus pneumonia.

In this report, we structurally and biochemically characterized the unknown gene product SP1746 from Streptococcus pneumoniae serotype 4. Various crystal structures of SP1746 in the apo form and in complex with different nucleotides were determined. SP1746 is a globular protein, which belongs to the histidine-aspartate (HD) domain superfamily with two Fe3+ ions in the active site that are coordinated by key active site residues and water molecules. All nucleotides bind in a similar orientation in the active site with their phosphate groups anchored to the diiron cluster. Biochemically, SP1746 hydrolyzes different nucleotide substrates. SP1746 most effectively hydrolyzes diadenosine tetraphosphate (Ap4A) to two ADPs. Based on the aforementioned data, we annotated SP1746 as an Ap4A hydrolase, belonging to the YqeK family. Our in vitro data indicate a potential role for SP1746 in regulating Ap4A homeostasis, which requires validation with in vivo experiments in bacteria in the future.

Microbial aetiology of community-acquired pneumonia in hospitalised adults: A prospective study utilising comprehensive molecular testing.

OBJECTIVES: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. METHODS: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analysed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. RESULTS: Of the 3238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. CONCLUSIONS: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard-of-care diagnostics alone.

Monitoring Over a Decade in the Serotype Prevalence of Streptococcus pneumoniae in Iran: A Systematic Review and Meta-analysis.

BACKGROUND: There is no comprehensive information about the circulating serotypes of Streptococcus pneumoniae in Iran in recent years. This study aimed to summarize information about the changes over a decade in the serotype prevalence of S. pneumoniae in Iran. METHODS: We performed a comprehensive search in PubMed/Medline, Web of Science, Science Direct, and the Iranian Database, such as Magiran and SID, from January 2011 to February 2023. The systematic process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was carried out by two researchers who were both independent and calibrated. Statistical analyses were carried out using Comprehensive Meta-Analysis software. Identifying and measuring heterogeneity were done using I2 and the chi-square test. Finally, Begg's rank correlation test was used in combination with a funnel plot to evaluate any possible publication bias. RESULTS: The search returned 16 relevant results, with a total of 1575 isolates. Of those studies, eight studies reported the distribution of S. pneumoniae serotypes among patients, three studies among healthy individuals, and five studies among both groups. As the meta-analysis revealed, the most common serotypes were 23F (n = 299, 14.1% [95% CI: 9.7-19.9]; I2 = 84.3%; P<0.001 for heterogeneity), 19F (n = 221, 13.4% [95% CI: 9.9-17.9; I2 = 76.7%; P<0.001 for heterogeneity]), and 19A (n = 102, 8.7% [95% CI: 6.5-11.7; I2 = 54.3%; P<0.001 for heterogeneity]). Moreover, Begg's test (P = 0.160, 0.173, and 0.176 for 23F, 19F, and 19A, respectively) showed no evidence of publication bias. CONCLUSION: Based on our pooled results, the majority of the serotypes of pneumococci in the Iranian population were 23F, 19F, and 19A, respectively, over the last decade. The findings can be valuable in selecting effective pneumococcal vaccine candidates and targeted antibiotics in Iranian patients.

Exploring Streptococcus pneumoniae capsular typing through MALDI-TOF mass spectrometry and machine-learning algorithms in Argentina: Identifying prevalent NON PCV13 serotypes alongside PCV13 serotypes.

Introduction: Laboratory surveillance of Streptococcus pneumoniae serotypes plays a crucial role in effectively implementing vaccines to prevent invasive pneumococcal diseases. The conventional method of serotyping, known as the Quellung reaction, is both time-consuming and expensive. However, the emergence of MALDI-TOF MS technology has revolutionized microbiology laboratories by enabling rapid and cost-effective serotyping based on protein profiles. Objectives: In this study, we aimed to investigate the viability of utilizing MALDI-TOF MS technology as an adjunctive and screening method for capsular typing of Streptococcus pneumoniae. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. Methods: Firstly, we established a comprehensive spectral database comprising isolates of serotypes present in the PCV13 vaccine, along with the top 10 most prevalent NON PCV13 serotypes based on local epidemiological data. This database served as a foundation for developing unsupervised models utilizing MALDI-TOF MS spectra, which enabled us to identify inherent patterns and relationships within the data. Our analysis involved a dataset comprising 215 new isolates collected from nationwide surveillance in Argentina. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. Results: Although our findings revealed suboptimal performance in serotype classification, they provide valuable insights into the potential of machine learning algorithms in this context. The sensitivity of the models ranged from 0.41 to 0.46, indicating their ability to detect certain serotypes. The observed specificity consistently remained at 0.60, suggesting a moderate level of accuracy in identifying non-vaccine serotypes. These results highlight the need for further refinement and optimization of the algorithms to enhance their discriminative power and predictive accuracy in serotype identification.By addressing the limitations identified in this study, such as exploring alternative feature selection techniques or optimizing algorithm parameters, we can unlock the full potential of machine learning in robust and reliable serotype classification of S. pneumoniae. Our work not only provides a comprehensive evaluation of multiple machine learning models but also emphasizes the importance of considering their strengths and limitations. Conclusion: Overall, our study contributes to the growing body of research on utilizing MALDI-TOF MS and machine learning algorithms for serotype identification purposes.

Group A Streptococcus Pneumonia in a Previously Healthy Individual: Is It Still a Thing?

Group A streptococcus (GAS) is known to cause many different kinds of infections, including invasive pneumonia in rare cases. When it is the causative agent, it is associated with a more severe disease course, but it can often be adequately treated if caught early enough. We hereby present the case of a 32-year-old male with no past medical history who presented with fever, hemoptysis, and tachycardia. Laboratory results showed leukocytosis, hyponatremia, mild transaminitis, and elevated creatine kinase. Initial imaging findings and clinical presentation were concerning for tuberculosis (TB) vs. community-acquired pneumonia (CAP), as it yielded a consolidation in the right upper lobe. The patient had no obvious risk factor except for imprisonment two years prior to symptoms onset. Empirical antibiotics and steroids were started. Quantiferon and acid-fast bacteria (AFB) were negative, but sputum and blood cultures were positive for Streptococcus pyogenes, ruling out TB. Antibiotic therapy was narrowed down. The patient responded well to therapy, with subsequent resolution of symptoms. The current body of knowledge regarding respiratory infections caused by GAS is limited by multiple factors, including its relative rarity and the diversity of how it can present, especially in a developed country. Its mimicry characteristics of other clinical entities, such as TB, can be deceiving, which can delay appropriate treatment if it occurs in settings where the diagnostic tools are not readily available. By sharing more cases and atypical presentations of this disease, the clinical presentations of this pathogen can be more fully understood, and it can be more rapidly identified and treated.

Nasopharyngeal carriage of Streptococcus pneumoniae serotypes among sick and healthy children in northern India: A case-control study.

BACKGROUND: Streptococcus pneumoniae is leading bacterial cause of community acquired pneumonia and according to World Health Organization, responsible for 14 % death in children. There is effective vaccine available against Streptococcus pneumoniae. Hence the primary objective was to isolate Streptococcus pneumoniae from nasopharyngeal swabs in children aged 2-59 months with and without community acquired pneumonia and to assess their serotypes. METHODS: This case-control study was conducted in tertiary teaching institutes in northern India. Hospitalized children, aged 2-59 months, with World Health Organization-defined community acquired pneumonia were included as cases. Age matched healthy controls were recruited from immunization clinic. All enrolments were done after written informed parental consent. Nasopharyngeal swabs were taken from both cases and controls, and were cultured on 5 % sheep blood agar with gentamycin plate for growth of Streptococcus pneumoniae and incubated in a jar at 370 for 18-24 hrs. Quellung reaction test was used for serotyping. RESULTS: From March 2017 to December 2022, 2693 children (1910 cases and 783 controls), were recruited. The median age of cases was 7 months and controls 10 months. Almost all the cases had received antibiotics prior to hospitalization. Streptococcus pneumoniae positivity in nasopharyngeal swab was 8.1 % in cases, of which 56.8 % were vaccine serotypes and 23.6 % in controls, of which 37.8 % were vaccine serotypes. Adjusted odds ratio of isolating vaccine serotypes among cases as compared to controls was 1.77 (95 % CI, 1.09-2.88). CONCLUSION: Streptococcus pneumoniae isolation from nasopharyngeal was found to be in lower proportion in cases as compared to control, though colonization with vaccine serotypes was higher in cases as compared to control. Therefore, pneumococcal vaccine coverage must be increased to prevent community acquired pneumonia.

Outcomes of pediatric community-acquired pneumonia before and after national pneumococcal immunization in Taiwan.

OBJECTIVE: In Taiwan, the incidence of invasive pneumococcal disease (IPD) in children declined after the catch-up primary vaccination programs and the full national immunization program (NIP) with PCV13. The objective of the study was to investigate the clinical outcomes of pediatric community-acquired pneumonia (CAP) before and after the NIP. METHODS: The study included patients aged 3 months to 17 years who were diagnosed with CAP and treated at the National Taiwan University Hospital between 2007 and 2019. Patients were assigned to three birth cohorts according to their birth years and vaccination eligibility: non-NIP, catch-up, and full NIP. We compared the rates of severe outcomes, including case fatality and pathogens. RESULTS: A total of 6557 patients who met the CAP criteria were enrolled during the study period. The case-fatality rate decreased from 3.2% (94/2984) in the non-NIP cohort to 0.3% (7/2176) in the catch-up cohort and 0.8% (11/1397) in the full NIP cohort (p < 0.001). Furthermore, there was a significant decrease in invasive ventilation from the non-NIP (17.9%) to both catch-up (6.8%) and full NIP cohorts (9.1%). The rate of IPD declined from the non-NIP cohort to the catch-up cohort (1.8% vs. 0.6%, p < 0.001) and from the catch-up to the full NIP cohort (0.6% vs. 0.07%, p = 0.014). In contrast, the rates of infections with other pathogens increased after NIP. CONCLUSION: The introduction of PCV13 showed significant reduction in case-fatality and IPD rates. The increasing rates of other pathogens warrant further surveillance for their clinical significance.

Meningitis and endocarditis as a sequela of streptococcus pneumonia mastoiditis: A case report.

Key Clinical Message: Austrian Syndrome classically consists of meningitis, endocarditis, and pneumonia due to Streptococcus pneumonia bacteremia. A literature review, however, does not show variants of this triad. Our case highlights a unique variant of Austrian Syndrome with mastoiditis, meningitis, and endocarditis which requires immediate recognition and treatment to prevent devastating patient outcomes. Abstract: Streptococcus pneumonia is responsible for more than 50% of all bacterial meningitis and has a case fatality rate of 22% in adults. In addition, Streptococcus pneumonia is also one of the most common causes of acute otitis media, a known cause of mastoiditis. However, in conjunction with bacteremia and endocarditis, limited evidence is able to be identified. This sequence of infections also closely relates to Austrian syndrome. Otherwise known as Osler's triad, Austrian syndrome is a rare phenomenon of meningitis, endocarditis, and pneumonia secondary to Streptococcus pneumonia bacteremia that was first delineated by Robert Austrian in 1956. The incidence of Austrian syndrome is reported to be less than <0.0001% per year and has decreased significantly since the initial usage of penicillin in 1941. Despite this, the mortality rate of Austrian syndrome is still around 32%. Despite an extensive literature review, we were unable to find any reported cases of variants of Austrian syndrome that include mastoiditis as the primary insult. As such, we present a unique presentation of Austrian syndrome with mastoiditis, endocarditis, and meningitis with complex medical management that led to resolution for the patient. To discuss the presentation, progression, and complex medical management of a previously undiscussed triad of mastoiditis, meningitis, and endocarditis occurring in a patient.

Emerging Antimicrobial Resistance.

The burden of emerging antimicrobial resistance (AMR) in the United States is significant and even greater worldwide. Mitigation efforts have decreased the incidence and deaths from antimicrobial-resistant organisms in the United States. Yet more than 2.8 million antimicrobial-resistant infections occur every year and more than 35,000 patients die as a result. Infection prevention and control, data tracking, antimicrobial stewardship, vaccines, therapeutics, diagnostics, and sanitation are all required to decrease AMR threats. In 2019, in the second version of the Centers for Disease Control and Prevention (CDC) report on antibiotic-resistant threats, the agency categorized AMR threats as urgent, serious, concerning, or to be watched. This review will discuss the following aspects of each bacterium in the CDC report: estimated numbers of cases and deaths, identify the better known and impactful mechanisms of resistance, diagnostic testing and its limitations, and current and possible future therapies. This review also presents anatomical pathology case examples that highlight the altered morphology of antibiotic partially treated bacteria in tissues.

A subunit vaccine against pneumonia: targeting Streptococcus pneumoniae and Klebsiella pneumoniae.

Community-acquired pneumonia is primarily caused by Streptococcus pneumoniae and Klebsiella pneumoniae, two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against S. pneumoniae and K. pneumoniae. The targeted proteins were the pneumococcal surface proteins (PspA and PspC) and choline-binding protein (CbpA) of S. pneumoniae and the outer membrane proteins (OmpA and OmpW) of K. pneumoniae. Different computational approaches and various immune filters were employed for designing a vaccine. The immunogenicity and safety of the vaccine were evaluated by utilizing many physicochemical and antigenic profiles. To improve structural stability, disulfide engineering was applied to a portion of the vaccine structure with high mobility. Molecular docking was performed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptors (TLR2 and 4). Further, the dynamic stabilities of the vaccine and TLRs complexes were investigated by molecular dynamics simulations. While the immune response induction capability of the vaccine was assessed by the immune simulation study. Vaccine translation and expression efficiency was determined through an in silico cloning experiment utilizing the pET28a(+) plasmid vector. The obtained results revealed that the designed vaccine is structurally stable and able to generate an effective immune response to combat pneumococcal infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13721-023-00416-3.

Chitosan loaded RNA polymerase inhibitor nanoparticles increased attenuation in toxin release from Streptococcus pneumonia.

Background: Multidrug-resistant (MDR) bacterial infections have become an emerging health concern around the world. Antibiotics resistance among S. pneumoniae strains increased recently contributing to increase in incidence of pneumococcal infection. This necessitates the discovery of novel antipnemococcal such as compound C3-005 which target the interaction between RNA polymerase and σ factors. Chitosan nanoparticles (CNPs) exhibited antibacterial activity including S. pneumonia. Therefore, the aims of the current investigation were to formulate CNPs loaded with C3-005 and characteristic their antimicrobial properties against S. pneumonia. Methods: The CNPs and C3-005 loaded CNPs were produced utilizing ionic gelation method, and their physicochemical characteristics including particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE%), and in vitro release profile were studied. Both differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were used for chemical characterization. The synthesized NPs' minimum inhibitory concentration (MIC) was determined using killing assay and broth dilution method, and their impact on bacteria induced hemolysis were also studied. Results: The NPs encapsulating C3-005 were successfully prepared with particle size of 343.5 nm ± 1.3, zeta potential of 29.8 ± 0.37, and PDI of 0.20 ± 0.03. 70 % of C3-005 were encapsulated in CNPs and sustained release pattern of C3-005 from CNPs was revealed by an in vitro release study. CNPs containing C3-005 exhibited higher antipnomcoccal activity with MIC50 of 30 µg/ml when compared with C3-005 and empty CNPs alone. The prepared C3-CNPs showed a reduction of bacterial hemolysis in a concentration-related (dependent) manner and was higher than C3-005 alone. Conclusions: The findings of this study showed the potential for using C3-005 loaded CNPs to treat pneumococcal infection.

Colonization, Density, and Antibiotic Resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13-Vaccinated Infants in the First Six Months of Life in Rochester, New York: A Cohort Study.

BACKGROUND: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat) nasopharyngeal colonization precedes disease pathogenesis and varies among settings and countries. We sought to assess colonization prevalence, density, Spn serotypes, and antibiotic resistance in children in the first 6 months of life in pediatric primary care settings. METHODS: Prospective cohort study in Rochester, NY during 2018-2020. Nasopharyngeal swabs were collected from 101 children at age 1, 2, and 3 weeks, then 1, 2, 4, 6, 9, 12, 15, 18, and 24 months. Spn serotypes were determined by Quellung. Oxacillin resistance for Spn and ß-lactamase production by Hflu and Mcat was tested. All children received PCV13 vaccine according to U.S. recommended schedule. RESULTS: Spn, Hflu, and Mcat colonization was detected in only 5% of infants before age 2 months old. Cumulative prevalence was 34% for Spn, 10% for Hflu, and 53% for Mcat in children ≤6 months of age. Nasopharyngeal bacterial density of Spn, Hflu, and Mcat (x = 2.71 log) in children ≤6 months of age was lower than at 7-24 months of age (x = 3.15 log, p < 0.0001). Predominant serotypes detected ≤6 months of age were 23B (16.7%), 22F (12.9%), 15B/C (11%), and 16F (9.2%). In total, 14.8% of Spn isolates were oxacillin resistant and 66.7% of Hflu isolates were ß-lactamase producing. CONCLUSION: Spn, Hflu, and Mcat nasopharyngeal colonization was uncommon and of low density among children ≤6 months old, especially among children <2 months of age. Non-PCV13 serotypes predominated and a different serotype distribution was observed in ≤6-month olds compared to 7- to 24-month olds.

Localization of cerebral vasculopathy following bacterial meningitis: What can we learn about postinfective ischemic sequelae?

Cerebrovascular complications of bacterial meningitis account for a high incidence of mortality and postinfective neurologic sequelae. Cerebrovascular complications occurring during acute bacterial meningitis are evident from angiographic evidence demonstrating arterial occlusion and vessel wall narrowing, histopathological studies demonstrating vessel wall changes, and radiographic studies demonstrating the presence of brain infarcts. Cerebrovascular disease during bacterial meningitis has been demonstrated in of Haemophilus influenzae, Streptococcus pneumonia, Group B Streptococcus, and Mycobacterium tuberculosis models of meningitis. Despite models of bacterial meningitis showing variable patterns of cerebral vasculopathy as a contributor to different aspects of postinfectious neurological decline, very few studies describe the predominant localization of cerebral vasculopathy with different meningitis causing pathogens. Thus, this review attempts to analyze the different locations of cerebral vasculopathic changes occuring in response to different microbial pathogens and provide a pathophysiologic basis for such an observation.

Serotipos y resistencia antimicrobiana de Streptococcus pneumoniae en población pediátrica china: una revisión de alcance

Esta revisión tuvo como propósito explorar la distribución de serotipos y la resistencia antimicrobiana de Streptococcus pneumoniae en la población pediátrica de China a partir de literatura publicada en los últimos seis años. Se realizó una revisión de alcance a partir de PubMed y dos bases de datos de China: CNKI y WanFang Data. Del total de 196 artículos extraídos, se seleccionaron 14 estudios para esta revisión. Hay 13 artículos que analizan la distribución de serotipos de Streptococcus pneumoniae; los serotipos más frecuentemente registrados son: 19F, 19A, 23F, 14 y 6B. Hay 11 artículos que analizan la resistencia antimicrobiana de Streptococcus pneumoniae, la prevalencia de no susceptibles a la penicilina se encuentra en el rango de 0 % a 95,7 %. Los aislados son muy resistentes a eritromicina, clindamicina, tetraciclina y trimetoprima-sulfametoxazol; son resistentes a penicilina en meningitis neumocócica pero son sensibles a penicilina en otras enfermedades neumocócicas, además, son muy sensibles a levofloxacina, vancomicina y Linezolid. Se concluye que la vacuna antineumocócica conjugada 13 tiene alta cobertura en los serotipos de Streptococcus pneumoniae en los niños de China continental, por eso se recomienda su inclusión en el programa de vacunación infantil; al mismo tiempo, se debe tener en cuenta la aparición de la sustitución de serotipos. Por eso, se deben incluir más pacientes pediátricos o niños en las investigaciones, especialmente los menores de cinco años. Es necesaria una vigilancia de alta calidad a largo plazo sobre la distribución de serotipos y resistencia antimicrobiana de Streptococcus pneumoniae para el desarrollo de la prevención de enfermedades neumocócicas.

This review aimed to explore the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Chinese pediatric population based on literature published in the last six years. A scoping review was performed using PubMed and two Chinese databases: CNKI and WanFang Data. Of the total of 196 articles extracted, 14 studies were selected for this review. There are 13 articles that analyze the distribution of Streptococcus pneumoniae serotypes, the most frequently registered serotypes are: 19F, 19A, 23F, 14 and 6B. There are 11 articles that analyze the antimicrobial resistance of Streptococcus pneumoniae, the prevalence of non-susceptible to penicillin is in the range of 0% to 95.7%. Isolates are highly resistant to erythromycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole; they are resistant to penicillin in pneumococcal meningitis but are sensitive to penicillin in other pneumococcal diseases, in addition, they are very sensitive to levofloxacin, vancomycin and Linezolid. It is concluded that the pneumococcal conjugate vaccine 13 has high coverage in Streptococcus pneumoniae serotypes in children from mainland China, therefore its inclusion in the childhood vaccination program is recommended; at the same time, the occurrence of serotype substitution should be taken into account. Therefore, more pediatric patients or children should be included in research, especially those under five years of age. Long-term, high-quality surveillance of the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae is necessary for the development of pneumococcal disease prevention.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23.

BACKGROUND: A new 20-valent pneumococcal conjugate vaccine (PCV20) provides protection against 20 pneumococcal serotypes. The vaccine has the potential to decrease the impact of pneumococcal diseases in society and to increase health among vulnerable persons. AIM: This study investigates the cost-effectiveness of vaccinating Danish adults in different age groups and risk of pneumococcal disease with PCV20 compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23) - either as PCV20 compared to PPV23 or as PPV23 followed by PCV20 compared to PPV23. METHODS: A Markov model adapted to the Danish setting was developed to estimate clinical outcomes and costs of vaccinating the Danish population in specific age and risk groups. The model used a restricted societal perspective and estimated outcomes and costs using a lifetime time horizon. To estimate the clinical outcomes and costs, inputs on vaccine effectiveness and waning were retrieved from other studies whereas data on risk groups, coverage and costs were based on real-world data. RESULTS: The results showed that in all scenarios the incidence and mortality of pneumococcal disease were reduced when vaccinating with PCV20, resulting in lower costs. For the vaccine target group of adults aged ≥18 years at moderate or high risk and all adults aged ≥65 years both in the case of PPV23+PCV20 compared to PPV23 and in case of PCV20 compared to PPV23 vaccination with PCV20 was found to be a dominant strategy gaining 1,350 or 5,821 quality-adjusted life years (QALYs), respectively, and reducing total costs by 60 or 396 million EUR, respectively, as compared to PPV23 vaccination alone. Similar results of dominant PCV20 strategy were found for other age and risk group comparisons. Both deterministic and probabilistic sensitivity analyses confirmed the results being robust to changes in input parameters and applied assumptions. LIMITATIONS: Like other modelling studies, this analysis has limitations such as lack of detailed data for some inputs. CONCLUSION: Vaccination with PCV20 reduced the incidence and mortality of pneumococcal diseases in Danish adults compared to PPV23. This reduction has the potential to reduce the financial burden related to managing diseases while also increasing public health.

Correlation of COVID-19 Receptors with Neutrophils and Their Role in the Adherence of Co-Infected Bacteria.

The COVID-19 caused by the SARS-CoV-2 virus has an impact on all aspects of patient care. Since the onset of this disease pandemic in 2019, numerous studies have been published which have attempted to identify virus receptors in the upper respiratory tract, such as nasal, oropharynx, and lung and their role in coinfection of bacterial adherence. In this study, the level of m RNA for platelet-activating factor receptor (PAF-R) and angiotensin-converting enzyme 2 receptor (ACE2-R) were detected in the whole blood of COVID-19 patients and controlled by using real-time reverse transcription-polymerase chain reaction technique. The results of the expression level of the PAF-R gene were higher in patients (43 ± 12.5) than in the healthy control (40 ± 2.1). Moreover, the expression level of ACE2-R was significantly (0.0001) increased in patients (27.5±6.2), compared to the control group. In addition, there was an elevation of neutrophils (79.6±17.6%) and PAF-R level (43%) in COVID-19 patients in comparison to the control (40) with a positive correlation between these factors (r=0.8769, P=0.0001). Nasopharyngeal epithelial cells showed a higher adherence rate (86%) to both bacteria isolates (Streptococcus pneumonia and Staphylococcus aureus) in patients than in the control group. Increased expression of PAF-R and ACE2-R genes in COVID-19 patients and co-infected bacteria disease could be the factors for the SARS-CoV-2 virus to enter the cells of the host.

Etiology, Diagnosis, Complications, and Management of Acute Otitis Media in Children.

Acute otitis media (AOM) is the most common infectious disease encountered by children under the age of two years and the most common cause of antibiotic use in children in the United States. AOM causes irritability, sleeplessness, decreased appetite, imbalance, and dizziness in patients, especially young children. This assessment was conducted to measure the effectiveness of surgical interventions in treating AOM. We reviewed the present findings regarding the etiology, clinical presentations, diagnosis, treatment, and surgical treatment of complications of AOM. Pain associated with AOM (otalgia) can be severe enough to cause parents to seek treatment for their infants or children. Various suggested measures have been used to treat AOM; antibiotic treatment with amoxicillin is still the treatment of choice for AOM, yet other antibiotics may be used in cases of allergy to penicillin or recent use of amoxicillin. Surgical intervention has been introduced and studied as a diagnostic, therapeutic, and preventive measure for AOM; nevertheless, a few studies have shown that surgical interventions are beneficial in treating and preventing AOM compared to the common practice of using antibiotics. Overdiagnosis of AOM is widespread, leading to injudicious antibiotic use, which contributes to antibiotic resistance. Further management should be determined together with the parent, particularly if observation is the primary intervention.

Encapsulated saponin by ferritin nanoparticles attenuates the murine pneumococcal pneumonia.

Streptococcus pneumonia is classified as a gram-positive bacterial pathogen that causes asymptomatic or symptomatic respiratory infections. This study aimed to evaluate the effects of designed encapsulated saponin by ferritin nanoparticles in the healing progression of experimental bacterial pneumonia. The saponin encapsulated by ferritin followed the disassembly-reassembly process. Pneumonia was induced by the preparation of Streptococcus pneumonia. A total of 50 NMRI mice were divided into control, pneumonia, pneumonia + ferritin, pneumonia + saponin, and pneumonia + encapsulated saponin by ferritin nanoparticles (Nano Saponin) groups. ELISA, Real-time PCR, and Western blotting were used to measure sera IL-4 level, tumor necrosis factor-alpha (Tnf-α), and protein cyclooxygenase-2 (COX-2) gene expression, respectively. COX-2 protein expression, Tnf-α gene expression, and serum levels of IL-4 reduced compared to the pneumonia group. The histopathology results revealed that the rates of inflammation, mucus secretion, pulmonary hemorrhage, thickening of the alveoli wall, and secretion of inflammatory cells were lower in the Nano Saponin group than in the other groups. This study suggests that Glycyrrhiza glabra saponin and encapsulated saponin by ferritin nanoparticles oral consumption with anti-Tnf-α effect besides decreasing protein expression of COX-2 allows mice with pneumonia to recover.

Cost-utility analysis of the universal pneumococcal vaccination programme for older adults in Norway.

The aim of this study was to establish whether the universal pneumococcal vaccination for older adults in Norway is likely to be cost-effective from the perspective of the health care provider. A decision tree model developed by the Public Health Agency of Sweden was adapted to the Norwegian setting. Two cohorts, consisting of 65-year-olds and 75-year-olds grouped into vaccinated and unvaccinated, were followed over a 5-year time horizon. In the base case, the 23-valent polysaccharide vaccine (PPV23) was used while the 13-valent pneumococcal conjugate vaccine (PCV13) was included in scenario analyses only. The costs and health benefits (measured in quality adjusted life years (QALY) gained) were compared in the two cohorts between the vaccinated and unvaccinated groups. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were not investigated. The relative importance of change in price was assessed by performing one-way sensitivity analyses. Under base-case assumptions, the programme for the 75-year-old cohort is expected to be dominant (cost-effective) from the health care perspective at the current maximal pharmacy retail price and at 75% vaccination coverage. In comparison, for the 65-year-old cohort the cost per QALY gained is approximately NOK 601,784 (EUR 61,281) under the base-case assumptions. A reduction in the cost of the vaccine to one quarter of its current level also brings the cost per QALY gained within the acceptable ranges in a Norwegian context for both the 65- and 75-year-old cohorts. There is no exact cost-effectiveness threshold in Norway. However, introducing a vaccination programme against pneumococcal disease for 65-year-olds in Norway is likely to fall within the acceptable range while for the 75-year-old cohort the universal programme appears to be dominant (cost-effective).

A Rare Case of Streptococcus Pneumoniae Causing Malignant Otitis Externa Complicated by Skull Base Osteomyelitis.

Skull base osteomyelitis is an aggressive infection involving bones of the skull. It is a rare complication of malignant otitis externa, caused by the contiguous spread of the infection. Patients are mostly elderly with comorbidities that compromise immunity. It is atypical for Streptococcus species to be encountered in basilar skull osteomyelitis. Here we present the case of an 80-year-old male with multiple comorbidities including diabetes mellitus with a two-month history of right ear pain associated with occasional discharge and diminished hearing who was found to have bacteremia and basilar skull osteomyelitis with Streptococcus pneumoniae isolated from blood and otorrhea fluid cultures. This unusual presentation of S. pneumoniae related skull base osteomyelitis could be attributed to an undiagnosed pancreatic cancer at the time of presentation. Malignant otitis externa can progress into invasive disease in the head and neck; almost all cases tend to be caused by Pseudomonas aeruginosa but unusual cases, such as this, can be caused by Streptococcus pneumoniae.